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Biomedical subjects

R McCarty

Publications and source records attributed to R McCarty.

At least 91 records · Page 5Linked to original sources
PubMed1985

Unilateral odor deprivation: effects on the development of olfactory bulb catecholamines and behavior.

The present studies began an examination of the process by which unilateral odor deprivation results in a 25% reduction in the size of the olfactory bulb. Rat pups had a single naris occluded on the day after the day of birth (Day 1) and were tested at several early postnatal ages. Dopamine (DA) levels were measured to gauge the effects of deprivation on a transmitter system which is intrinsic to the bulb, while norepinephrine (NE) concentrations were assessed to determine how deprivation affects inputs to the bulb from higher brain regions. A significant reduction in DA concentration (pg/mg protein) was observed on Day 8 and persisted until Day 30 although protein concentrations (pg/mg bulb) were not affected. In contrast, deprivation did not significantly alter NE concentration. Deprived and control pups did not differ on a series of behavioral and morphometric measures, suggesting that the surgical procedure did not seriously impair normal growth patterns. The results indicate that unilateral naris occlusion induces rapid and specific changes within the olfactory bulb.

Animals↗
PubMed1985

Cardiovascular responses to acute footshock stress in adult and aged Fischer 344 male rats.

Tail artery catheters were surgically implanted in Fischer 344 male rats to allow for measurement of mean arterial pressure (MAP, mm Hg) and heart rate (HR, beats/min) in conscious, unrestrained rats. Basal values of MAP and HR were similar for groups of 4, 12 and 24 month old rats. Increments in Map did not differ among rats of the 3 ages following handling and transfer to a shock chamber or immediately or 5 minutes after exposure to inescapable footshock (2.0 mA, 0.6 sec duration, every 6 sec for 1 min). In contrast, there was a significant age-related attenuation of the tachycardia following handling and transfer of rats to the shock chamber and at the end of footshock. These data are consistent with previous findings of a reduced sensitivity of the aged myocardium to stress-induced sympathetic stimulation.

Aging↗
PubMed1985

Enhanced sympathetic-adrenal medullary response to cold exposure in spontaneously hypertensive rats.

To investigate the regulation of sympathetic-adrenal medullary function in spontaneously hypertensive (SHR) male rats, we measured urinary catecholamine excretion for 4 h at room temperature and also during cold exposure (4 degrees C) in groups of four and 12-week-old stroke-prone SHR (SHRSP), stroke-resistant SHR (SHRSR) and normotensive Wistar-Kyoto (WKY) rats. The effect of cold exposure on 12-week-old adrenal denervated rats was also examined. At room temperature, urinary excretion of epinephrine, but not norepinephrine or dopamine, was increased significantly in four-week-old SHRSP and SHRSR rats compared with age-matched WKY. The enhanced excretion of epinephrine at room temperature was not observed in hypertensive rats at 12 weeks of age. During cold exposure, urinary concentrations of each catecholamine increased markedly in rats of all three strains. In addition, the epinephrine response was significantly enhanced in SHRSP rats and the norepinephrine, epinephrine and dopamine responses were significantly enhanced in SHRSR rats. Following adrenal denervation, the urinary epinephrine response to cold exposure was abolished in all strains. These results reveal an enhancement of sympathetic and neurally-mediated adrenal medullary responses in prehypertensive SHR rats and a greater urinary epinephrine response to cold exposure in four and 12-week-old SHR rats. This alteration in catecholamine secretion may be important in the development and maintenance of this type of experimental hypertension.

Adrenal Medulla↗
PubMed1984

Effects of 2-deoxyglucose on plasma catecholamines in adult and aged rats.

To examine the effects of aging on the responsiveness of the sympathetic-adrenal medullary system, I have measured plasma levels of norepinephrine (NE) and epinephrine (EPI) in adult (6 months old) and aged (24 months old) Fischer 344 male rats. Two days prior to testing, rats were surgically prepared with chronic tail artery catheters to permit remote sampling of blood in conscious, unrestrained animals. Following collection of basal blood samples, each rat received a single injection of 2-deoxyglucose (2-DG, 250 or 500 mg/kg, IP) and additional blood samples were collected 1, 2 and 4 hours later. 2-DG, a glucose analogue, stimulates a centrally mediated activation of the adrenal medulla and to a lesser extent the postganglionic sympathetic neurons. For purposes of analysis, data were excluded from animals which died within 4 hours after injection. Basal plasma levels of both catecholamines were similar in adult and aged rats. Administration of 2-DG was attended by significant and sustained increases in plasma NE and EPI in rats of both ages. A greater proportion of aged rats died following administration of 2-DG compared to adult rats. At the higher dose of 2-DG, plasma levels of NE were significantly higher in 6 month old rats at 1 and 2 hours post-injection. In contrast, plasma levels of EPI were significantly higher in 24 month old rats at 1 and 2 hours after administration of 250 mg/kg 2-DG and at 1 hour after administration of 500 mg/kg 2-DG.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Medulla↗
PubMed1984

Strain differences in sympathetic-adrenal medullary responsiveness and behavior.

Three experiments confirmed and extended previous findings from this laboratory regarding strain differences in physiological and behavioral responses of rats to stressful stimulation. In the first experiment, adult male Wistar-Kyoto (WKY) rats had greater plasma levels of norepinephrine and epinephrine and higher mean arterial pressures following 5 min of intermittent footshock (2.0 mA, 0.5-sec duration, every 6 sec) compared to adult male Brown-Norway (B-N) rats. In contrast, basal plasma levels of both catecholamines and resting values of mean arterial pressure and heart rate did not differ between strains when rats were undisturbed in their home cages. The second experiment involved a behavioral comparison of adult male and female WKY and B-N rats during 3 consecutive daily tests in an open field arena. B-N males and females were dramatically more active and reared more frequently during each open field test compared to WKY rats. For the third experiment, adult male and female rats of the two strains were trained in a one-trial passive avoidance task and median crossover latencies were similar for all strain-sex comparisons. However, median 24-hr retention latencies were much greater for WKY male and female rats. These findings indicate that strain differences in the physiological and behavioral responses of WKY and B-N rats are consistent across sexes. Moreover, our studies with these inbred strains of rats provide a convenient model for examining the relationship between sympathetic-adrenal medullary activity and behavioral responses to stressful stimulation.

Adrenal Medulla↗
PubMed1984

Dopamine may be a neurohormone in rat adrenal cortex.

In the periphery, dopamine (DA) is a precursor for norepinephrine (NE) and epinephrine (EPI) biosynthesis and is itself a neurotransmitter in sympathetic ganglia. In addition, DA may function as a neurohormone in providing maximum tonic inhibition of aldosterone secretion from the adrenal cortex. We have quantified the catecholamine content of the adrenal gland and have examined factors that regulate DA content of the adrenal cortex. Adult male Sprague-Dawley rats were assigned to one of four groups: adrenal demedullated (ADM); adrenal denervated via splanchnic nerve section (ADN); adrenal demedullated-denervated (DMN); and sham-operated controls (Sham). Ten days after surgery, rats were killed by decapitation, and the adrenals were removed and later assayed for catecholamine content. Compared with Sham, ADM and DMN decreased NE and EPI levels by 92-99% but DA levels by only 57-58%. ADN decreased levels of each catecholamine by 18-26%. These findings indicate that the adrenal cortex contains approximately 40% of the total gland content of DA and less than 8% of the total gland content of NE and EPI. Furthermore, DA in the adrenal cortex does not appear to require an intact splanchnic nerve supply to the adrenal. In a second experiment, we examined the effects of inhibition of catecholamine biosynthesis with alpha-methyl-p-tyrosine (alpha-MPT) on DA content in Sham and ADM rats. In Sham rats, alpha-MPT decreased adrenal DA by 44% and heart NE by 37%. In contrast, treatment of ADM rats with alpha-MPT increased adrenal DA by 49% but decreased heart NE by 36%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex↗
PubMed1983

Plasma catecholamines in fasted and sucrose supplemented rats.

Rats were food deprived or given a sucrose supplemented diet for 3 days. Resting plasma catecholamine levels measured remotely from undisturbed rats were not altered by either dietary treatment. However, food deprivation did result in decreases in resting mean arterial blood pressure, heart rate, plasma volume and plasma Na+ concentration. After one minute of intermittent footshock food deprived and sucrose fed rats did not differ from controls with respect to blood pressure, heart rate or plasma catecholamine levels but food deprived rats were less active during footshock and had lower levels of plasma glucose immediately after footshock when compared to controls or sucrose fed rats. Food deprivation and dietary sucrose supplementation have been shown to alter norepinephrine (NE) turnover in specific sympathetic target tissues. Our data indicate that these changes in turnover are not reflected by changes in plasma NE. Therefore, NE turnover rates and plasma NE concentration may not be equivalent indices of sympathetic activity.

Adrenal Medulla↗
PubMed1983

Choline administration: lack of effect on plasma catecholamines in rats.

Choline chloride (35 or 70 mg/kg, IP) or saline was administered daily for 3 consecutive days to adult male Sprague-Dawley rats. Before and 30, 60 and 120 minutes after the third injection of choline chloride or saline, blood samples were collected from a chronic tail artery catheter and later analyzed for levels of norepinephrine (NE) and epinephrine (EPI). Plasma levels of both catecholamines did not differ between choline- and saline-injected rats at either of the four sampling points. When insulin (10 IU/kg, SC) was administered to stimulate the sympathetic-adrenal medullary system reflexly, plasma levels of NE and EPI increased significantly above basal values but were similar for choline- and saline-injected rats. These findings do not support a role for choline availability in the regulation of catecholamine secretion from the adrenal medulla.

Animals↗
PubMed1983

Adaptation to stress: tyrosine hydroxylase activity and catecholamine release.

The effects of adaptation to stress and of genetic differences on levels of in vitro tyrosine hydroxylase (TH) activity and in vivo catecholamine (CA) release are reviewed. It is shown that adaptation of animals to a wide variety of stressors including immobilization, electroconvulsive shock, footshock, hemorrhage, exercise and cold exposure results in a reduced CA response in the plasma, brainstem and heart to subsequent exposure to the same stress. Adaptation to many of the latter stressors also produces increased in vitro levels of TH activity. A similar inverse relation between in vitro TH activity and in vivo CA release is described for two inbred rat strains which differ in emotionality (Brown-Norway and Wistar Kyoto). The inverse relationship between TH activity and CA release may reflect different processes of biochemical adaptation utilized either for acclimation to stress, for preparation for emergency reactions or for changes in the metabolic costs of transmitter release. The similarity between environmental and genetic effects on these variables suggests that the above changes have a common adaptive function.

Adaptation, Psychological↗
PubMed1983

Stress, behavior and experimental hypertension.

Over the past twenty-five years, several animal models of human essential hypertension have been produced through the development of inbred strains or lines of laboratory rats. The general availability of laboratory rats with genetically determined increases in arterial blood pressure has stimulated an impressive volume of research in the pathophysiology of experimental hypertension. In contrast, relatively little attention has been devoted to the study of behavioral correlates of experimental hypertension. In this review, I will evaluate the advantages and limitations of studying animal models of essential hypertension. Emphasis will then be placed on the relationship between stressful stimulation and behavioral and physiological responsiveness in two animal models of essential hypertension. Specifically, studies from my laboratory have examined sympathetic nervous system activity and behaviors of rats under basal conditions and following acute or chronic exposure to stressful stimulation. These findings indicate that the spontaneously hypertensive (SHR) strain is excessively responsive behaviorally and physiologically to a variety of stressful stimuli when compared to its Wistar-Kyoto (WKY) normotensive control strain. In contrast, the behavioral and physiological responses of New Zealand genetically hypertensive (GH) and normotensive (N) rats do not differ following acute exposure to stress. Thus, the hyperreactivity of SHR rats to stressful stimulation is not necessarily related to the development of hypertension but may be a valuable marker of the predisposition to develop high blood pressure in rats of the SHR strain. An experimental approach is outlined for examining the causal relationship between a genetically determined physiological or behavioral marker and the development of hypertension.

Adrenal Medulla↗
PubMed1983

Increased adrenal catecholamines in salt-sensitive genetically hypertensive Dahl rats.

Catecholamine levels and activity of catecholamine-forming enzymes have been quantitated in adrenal glands of Dahl sodium-resistant (R) and sodium-sensitive (S), genetically hypertensive rats maintained on low- or high-salt diets. A high-salt diet results in markedly different changes in the catecholamine metabolism in R and S rats. In R rats, a high-salt diet reduces the activities of tyrosine 3-hydroxylase (TH;-5%) and dopamine beta-hydroxylase (DBH; -18%) as well as the levels of all catecholamines (dopamine -28%, norepinephrine -11%, and epinephrine -28%). In contrast, S rats fed a high-salt diet showed increased TH (+7%) and phenylethanolamine N-methyltransferase (+16%) activities as well as an increased content of adrenal norepinephrine (+13%) and epinephrine (+21%). These findings demonstrate a genetic difference in the effects of a high-salt diet on the synthesis of catecholamines in the adrenal gland of Dahl R and S rats. Hypertension only occurs in S rats on a high-salt diet, concomitant with large increases in the formation of adrenal catecholamines.

Adrenal Cortex↗
PubMed1983

Neonatal hyperthyroidism: effects on sympathetic responses to stress in adult rats.

Treatment of developing rats with thyroid hormone results in accelerated maturation of sympathetic and adrenal medullary responses to reflex activation of central sympathetic outflow. In this study, we examined the effects of neonatal hyperthyroidism on the responsiveness of the sympathetic nervous system of adult rats to acute stress. Hyperthyroidism was produced in Long-Evans hooded rats by injections of thyroxine (neo-T4, 1 mg/kg body wt) on postnatal days 1-4. Littermate controls received injections of vehicle only. In adulthood, male rats of the two groups were prepared with chronic tail artery catheters to allow repeated sampling of blood and direct measurements of mean arterial pressure (MAP, mmHg) and heart rate (HR, beats/min). Two days after surgery, rats were stressed by exposure to 1 min of inescapable foot shock (2.0 mA, 0.6-s duration, every 6 s). The activity of the sympathetic nervous system was assessed by measuring plasma levels of norepinephrine (NE) and epinephrine (E). Basal plasma levels of NE and E and resting MAP did not differ between neo-T4 and control rats. However, basal HR was elevated in neo-T4 rats. Footshock-induced increments in plasma levels of both catecholamines were greater in neo-T4 compared with control rats even though behavioral responses to footshock were similar across groups. However, neo-T4 rats were more active when tested in an open field on each of 3 consecutive days. These findings indicate that neonatal treatment with T4 results in hyperresponsiveness of the sympathoadrenal medullary system to acute stress that persists into adulthood.

Animals↗
PubMed1983

Vasodilator responses to cholinergic and adrenergic stimulants in spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) normotensive rats.

The cardiovascular effects of isoprenaline, methacholine, and sodium nitroprusside were studied in spontaneously hypertensive (SHR) and in Wistar-Kyoto normotensive (WKY) rats. In conscious rats with chronic indwelling arterial cannulae, methacholine caused a much greater fall in mean arterial blood pressure (MAP) in SHR rats, abolishing the initial 30-40 mm Hg difference in MAP at a dose of 2.5 micrograms/kg. The hypotensive response to methacholine was accompanied by reflex tachycardia in WKY rats but by a dose-related bradycardia in SHR rats. Isoprenaline increased heart rate and reduced blood pressure to a similar extent in rats of both strains. Administration of sodium nitroprusside resulted in a hypotensive response that was of greater duration in SHR rats. In addition, the reflex tachycardia was more marked and of greater duration in WKY compared to SHR rats. This demonstrates that the baroreflex response to vasodilation is suppressed in SHR rats and that this may contribute to the increased vasodepressor response of these animals to methacholine. However, when baroreflexes but not initial MAP were suppressed with pentobarbital, methacholine caused a similar degree of bradycardia in SHR and WKY rats but a greater vasodepressor response in SHR rats. With isoprenaline, the MAP difference between strains was maintained at all doses up to 200 ng/kg. Although it is not yet clear what is responsible for the increased vascular constriction of SHR rats, our findings suggest that it can be removed by muscarinic receptor activation with methacholine but not by stimulation of beta-adrenoceptors.

Animals↗
PubMed1982

Physiological and behavioral responses of New Zealand hypertensive and normotensive rats to stress.

A chronic catheter was inserted into the ventral tail artery of adult male New Zealand hypertensive (NZH) and normotensive (NZN) rats to allow for repeated sampling of blood and measurement of blood pressure and heart rate in conscious animals without handling. Two days after surgery, plasma levels of norepinephrine (NE) and epinephrine (EPI) were similar in NZH and NZN rats while resting and undisturbed in their home cages. Mean arterial blood pressure was significantly higher in NZH rats (166 +/- 9 mm Hg) than in NZN rats (124 +/- 4 mm Hg) but basal heart rates did not differ (345 +/- 8 and 342 +/- 14 beats/min, respectively). Increments in plasma levels of NE and EPI and in mean arterial blood pressure and heart rate were similar in NZH and NZN rats following transfer to a shock box and immediately and 10 minutes after exposure to 1 minute of intermittent footshock. Male rats of the two strains also did not differ in their behaviors during tests in an open field arena. These results indicated that NZH and NZN rats do not differ with respect to basal or stress-induced increments in sympathetic-adrenal medullary activity or in several behavioral measures. These results are in striking contrast to previous studies with the Okamoto strain of spontaneously hypertensive (SHR) rats and indicate that genetically determined increases in arterial blood pressure are not necessarily associated with sympathetic-adrenal medullary and behavioral hyperresponsivity to stress.

Animals↗